To understand the relationship between hypertension and insulin resistance we are studying insulin signal transduction pathways related to nitric oxide production in vascular endothelium. Human forearm blood flow studies suggest that physiological concentrations of insulin can cause vasodilation of small vessels via the production of nitric oxide by endothelial cells. Furthermore, the degree of insulin sensitivity exhibited for this vasodilatory response is positively correlated with insulin sensitivity for glucose uptake. This suggests that insulin signaling pathways may be related to nitric oxide production in vascular endothelium. Thus, insulin resistance may contribute to the pathogenesis of hypertension under some conditions. We recently obtained a nitric oxide meter that is capable of directly measuring nitric oxide at nanomolar concentrations. We are using this device to characterize the insulin response of human umbilical vein endothelial cells (HUVEC) in primary culture. We will use insights gained from our adipose cell transfection studies to dissect insulin signaling pathways related to nitric oxide production in vascular endothelium using various transfection techniques.